To our knowledge, only a few studies have simultaneously investigated the bidirectional association between type 2 diabetes and depression, but the results are. Question. Is the type 2 diabetes depression relation bi-directional? Bidirectional association between depression and type 2 diabetes mellitus in women. OBJECTIVE Epidemiological studies have repeatedly investigated the association between depression and metabolic syndrome (MetS). However, the results.
The remaining 80 control subjects either received a placebo or metformin. Pioglitazone achieved superior improvements in depressive symptoms mean difference, 3. Importantly, the improvement in depressive symptoms was higher in the subgroup of patients without metabolic comorbidities OR, 5.
The observed association was independent of depression severity at baseline and of any concomitant medication [ 41 ]. However, the inclusion of only mild- to moderately depression patients may have limited the results of this study, as the biased exclusion of patients with severe depression harbors the risk of overestimating the effects of metformin treatment [ 42 ]. These mechanisms include shared inflammatory pathways, dysfunction of the hypothalamic-pituitary-adrenal HPA axis, common metabolic effectors like leptin, in addition to a host of environmental, genetic, and behavioral factors.
Inflammation A growing body of evidence indicates that inflammation is a key shared factor in the bidirectional relationship between depression and T2DM and it has been implicated in the development of both diseases.
The meta-analysis by Haapakoski et al. Moreover, the relationship between inflammation and the risk of future depression was studied by Khandaker et al. In contrast, the role of inflammation in diabetes was extensively validated in a meta-analysis of 19 cohort and nested case-control studies, which found that elevated levels of CRP predicted the development of T2DM RR, 1.
The work of Au et al. After approximately 6 years of follow-up, two observations were made. Second, after adjustments for comorbidities and body mass index BMIthe risk of incident T2DM in participants with elevated depressive symptoms and high CRP levels was attenuated; however, it remained significant adjusted HR, 2.
The Bidirectional Relationship Between Depression & Diabetes
The findings of this study strongly indicate that general immune activation may not be linked to depressive symptoms, but rather to specific inflammatory profiles.
However, the lack of a nondiabetic control group may have critically limited the practical implications of these findings [ 47 ]. Hypothalamic-Pituitary-Adrenal Axis Ample evidence exists to support the involvement of the HPA axis in the pathogenesis of both depression and diabetes. One meta-analysis found that depression was associated with dysregulation of the HPA axis, resulting in higher cortisol and adrenocorticotropic hormone levels, and lower corticotropin-releasing hormone levels [ 48 ].
Other studies have supported the role of HPA axis dysregulation in diabetes, as diabetes patients were found to have higher levels of cortisol before and after the dexamethasone suppression test [ 49 ], as well as a flatter diurnal cortisol curve with evidence of a blunted cortisol awakening response and a less steep slope throughout the day [ 50 ]. To the contrary, the longitudinal cohort study by Spanakis et al.
There was a problem providing the content you requested
In an effort to explain the relationship between cortisol levels, insulin resistance, and depression, Yokoyama et al. No significant difference was observed in the peak cortisol values or the insulin resistance index between the two groups. Despite such evidence, and to the best of our knowledge, there have been no sound clinical studies exacting the role of HPA axis dysregulation in the comorbidity of diabetes and depression.
Leptin Other researchers have suggested a role for leptin in the association between depression and diabetes. Leptin is a protein that is mainly produced by adipocytes and is responsible for the regulation of appetite, energy, and body fat and water composition [ 54 ]. Moreover, Chirinos et al. Similarly, the role of leptin in diabetes was supported by a meta-analysis of 11 prospective studies by Chen et al.
The authors reported a significant association between leptin and an increased risk of T2DM in a sex-specific manner, where elevated leptin levels were related to an increased risk of T2DM in men RR, 1. To investigate the role of leptin in depression associated with diabetes, levels of leptin were recently measured by Haleem et al.
The study found a weight-dependent increase in leptin levels in diabetes patients with and without depression.
Notably, none of the differences were significant in women [ 58 ]. Genetic Factors Several studies have attempted to explain the relationship between depression and diabetes through the presence of a common genetic variant that predisposes individuals to both conditions.
For example, 20 single-nucleotide polymorphisms SNPs previously reported to be linked with the risk of T2DM were tested for their association, independently or in combination, with T2DM or MDD in a cross-sectional cohort of 17, individuals [ 59 ]. Individuals who were enrolled in this study had a baseline assessment of their T2DM status using the oral glucose tolerance test and were diagnosed with major depression according to the DSM 4 diagnostic criteria.
Bidirectional Association between Depression and Type 2 Diabetes in Women
In their analysis, only the A allele of rs was negatively associated with MDD. Based on the results of the aforementioned studies, it is difficult to establish a genetic basis for the relationship between T2DM and MDD. The present findings support the pressing need for long, outcome-oriented, randomized clinical trials to determine whether the identification and treatment of patients with these comorbid conditions will improve their medical outcomes and quality of life, and possibly have beneficial effects on both mood and glycemic control.
This review also endorses the concept of integration of mental health assessment in primary health care systems, particularly in the domain of diabetes. Similarly, we recommend frequent screening for diabetes in patients with depression.
This, consequently, will aid in the early detection and improved management of this chronic debilitating condition. In addition, a more precise understanding of the underlying mechanisms of this bidirectional relationship would ideally open the door for new and advanced therapeutic and preventive options for both conditions in the near future.
Footnotes No potential conflict of interest relevant to this article was reported. Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome in people with severe mental illnesses: Diagnostic and statistical manual of mental disorders: American Psychiatric Association; Prevalence of depression in adults with diabetes: The prevalence of comorbid depression in adults with diabetes: The prevalence of comorbid depression in adults with Type 2 diabetes: Type 2 diabetes and depressive symptoms in older adults: Mental disorders among persons with diabetes: Association between major depression and type 2 diabetes mellitus: Depression and type 2 diabetes in low- and middle-income countries: Diabetes Res Clin Pract.
Type 2 diabetes mellitus as a risk factor for the onset of depression: A prospective study of type 2 diabetes and depressive symptoms in the elderly: The role of depression and anxiety in onset of diabetes in a large population-based study.
Examining a bidirectional association between depressive symptoms and diabetes. Depression and type 2 diabetes over the lifespan: Quantitative assessment of the bidirectional relationships between diabetes and depression.
Type 2 diabetes in patients with major depressive disorder: Therefore, temporal relationship has attracted much attention in the past few years.
The cohort has been followed every 2 years with mailed questionnaires that update exposure information and inquire about newly diagnosed medical illnesses. Details have been published elsewhere.
Participants with no information on depression status at baseline antidepressant medication use: Therefore, participants were left for the current analyses. Depression Measurement Self-reported symptoms of depression, use of antidepressant medication and doctor diagnosed depression were used as measures of depression.
Depressive symptoms were assessed in, and with the Mental Health Index MHI-5a five-item subscale of the Short-Form 36 Health Status Survey designed to capture psychological distress versus well-being. The scale was scored from 0 towith lower scores indicating more severe depressive symptomatology SDS. The MHI-5 has been shown to have high sensitivity and specificity for major depression, with an area under the receiver-operating characteristic curve of 0. This information was updated biennially through The type of antidepressant use was first inquired inwhen participants were asked to specifically report their regular use during the past 2 years of selective serotonin reuptake inhibitors SSRIs, including fluoxetine, sertraline, paroxetine, citalopramor other antidepressants, of which the tricyclic antidepressants TCAs amitriptyline, imipramine, and nortriptyline were provided as examples.
This information was updated every two years thereafter. The nurses were first asked whether they ever or before, —,had physician-diagnosed depression in This information was also updated biennially. Therefore, clinical depression was defined as reported a physician-diagnosed depression or antidepressant use. For the analysis of whether depression increased the risk of developing diabetes, we created a proxy measure for depressive symptoms severity utilizing the MHI-5 score and clinical depression information.
The participants were categorized into four groups: Assessment of Diabetes A supplementary questionnaire regarding symptoms, diagnostic tests, and hypoglycemic therapy was mailed to women who indicated on any biennial questionnaire that they had been diagnosed as having diabetes. Several repeated mailings were sent to non-respondents, and these were followed by telephone interviews. A case of diabetes was considered confirmed if at least one of the following was reported on the supplementary questionnaire according to the National Diabetes Data Group criteria: For cases of type 2 diabetes identified after Junewe lowered the cut-off point to 7.
The Bidirectional Relationship between Diabetes and Depression: A Literature Review
Height and weight were ascertained on the enrollment questionnaire, and weight was further requested every two years thereafter. The questionnaire also updated the information on cigarette smoking non-smokers, past smokers and current smokers. The presence of a family history of diabetes in first-degree relatives was assessed inand Marital status was inquired inand Physical activity was measured biennially except with the use of a validated questionnaire.
Participants were asked to report the hours spent per week on moderate e. We asked how often, on average, a participant had consumed a particular amount of a specific type of food during the previous year.